The overall goal of this project is to test a meal replacement beverage that will ultimately preserve muscle loss during calorie restriction weight loss (CRWL) in obese older individuals. We previously developed a meal replacement rich with a proprietary blend of essential amino acids (TMR) that was more than three times as effective as whey protein in stimulating muscle protein synthesis (MPS) in the elderly. Utilizing this TMR and protein intake based on minimal protein requirements (0.8 gm protein/kg/day), we demonstrated a greater reduction in adipose tissue compared to a competitive meal replacement. Even so, volunteers still lost some muscle mass using the TMR. This likely reflected the fact that the optimal protein intake in older individuals is significantly greater thn 0.8 g/kg/day, and the hypocaloric condition of CRWL further elevated the need for optimal protein. In our formulation (MyoEon), we have now increased the absolute amount of EAAs and also included citrulline to even further promote the availability of EAAs to skeletal muscle. Although MyoEon is sufficiently developed for testing the central hypothesis of this project, part of this Phase 1 project will be to further optimize several aspects of product. The overarching hypothesis of this proposal is that the ingestion of MyoEon will foster an improvement in net protein synthesis, through an increased rate of protein synthesis and a decreased rate of protein breakdown as compared to a commercially available high protein meal replacement (Bariatric Advantage). Specific Aim 1: We will optimize the palatability and cost for ingredients, production, packaging, and fulfillment, which will validate the hypothesis that MyoEon can be profitably sold in retail markets. We will work directly with our food science partner (Mattson, Inc., Foster City, CA; http://www.foodcom.com/) to establish the criteria of acceptance for the formulation of MyoEon. The metric of success will be defined by establishing the feasibility of MyoEon as a palatable (determined by focus groups) and cost effective (total costs per product less than $1.00) product for use in weight loss. Specific Aim 2: We will demonstrate the feasibility of MyoEon to preserve lean body mass during CRWL as compared to Bariatric Advantage, through increased net protein synthesis, calculated as the difference between protein synthesis and breakdown determined by stable isotope tracer methodology. Demonstration that MyoEon is superior to the highest quality competitor will represent the metric of success for this aim and serve as the mechanistic underpinning for a Phase II randomized, clinical trial (RCT) performed in conjunction with the Mountain West Clinical Translational Research - Infrastructure Network. In this RCT, we will establish the effectiveness of MyoEon vs Bariatric Advantage in an outcome study focused on maintenance of muscle mass and improvement of functional capacity, as well as amplification of the metabolic benefits of weight loss.